Chimeric capsids
The present invention relates to viral vectors and methods of their production and use.
1. An adeno-associated virus (AAV) particle comprising a capsid protein, said capsid protein comprising a chimeric polypeptide which has at least 95% identity with a reference sequence comprising SEQ ID NO: 435; wherein the chimeric polypeptide is a substitutional variant of SEQ ID NO: 435; and wherein the chimeric polypeptide comprises one or more donor sequences, said one or more donor sequences selected from SEQ ID NOs: 465, 467-470, 548-553, and fragments of at least 4 amino acids thereof.
2. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NOs: 469, 552, and fragments of at least 4 amino acids thereof.
3. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NOs: 470, 548, and fragments of at least 4 amino acids thereof.
4. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NO: 550, and fragments of at least 4 amino acids thereof.
5. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NO: 549, and fragments of at least 4 amino acids thereof.
6. The AAV particle of claim 1 , comprising a vector genome which comprises at least one payload region, wherein said payload region encodes a therapeutic protein for treatment of a neurological disease, disorder, and/or condition.
7. The AAV particle of claim 1 , comprising a vector genome which comprises at least one payload region, wherein said payload region encodes an siRNA, an shRNA, a miRNA, or a precursor thereof.
8. The AAV particle of claim 7 , wherein said payload region encodes an siRNA or a precursor thereof.
9. The AAV particle of claim 7 , wherein said payload region encodes an miRNA or a precursor thereof.
10. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NO: 553, and fragments of at least 4 amino acids thereof.
11. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NO: 467, and fragments of at least 4 amino acids thereof.
12. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NOs: 468, and fragments of at least 4 amino acids thereof.
13. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NOs: 465, and fragments of at least 4 amino acids thereof.
14. The AAV particle of claim 1 , wherein said one or more donor sequences are selected from SEQ ID NOs: 551, and fragments of at least 4 amino acids thereof.
15. The AAV particle of claim 1 , wherein said chimeric polypeptide has at least 97% identity with the reference sequence comprising SEQ ID NO: 435.
16. The AAV particle of claim 1 , wherein said chimeric polypeptide has at least 99% identity with the reference sequence comprising SEQ ID NO: 435.
17. An adeno-associated virus (AAV) capsid protein, said AAV capsid protein comprising a chimeric polypeptide which has at least 95% identity with a reference sequence comprising SEQ ID NO: 435; wherein the chimeric polypeptide is a substitutional variant of SEQ ID NO: 435; and wherein the chimeric polypeptide comprises one or more donor sequences selected from SEQ ID NOs: 465, 467-470, 548-553, and fragments of at least 4 amino acids thereof.
18. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 465 and fragments of at least 4 amino acids thereof.
19. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 467 and fragments of at least 4 amino acids thereof.
20. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 468 and fragments of at least 4 amino acids thereof.
21. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NOs: 469, 552, and fragments of at least 4 amino acids thereof.
22. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NOs: 470, 548, and fragments of at least 4 amino acids thereof.
23. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 549 and fragments of at least 4 amino acids thereof.
24. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 550 and fragments of at least 4 amino acids thereof.
25. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 551 and fragments of at least 4 amino acids thereof.
26. The AAV capsid protein of claim 17 , wherein said one or more donor sequences are selected from SEQ ID NO: 553 and fragments of at least 4 amino acids thereof.
27. The AAV capsid protein of claim 17 , wherein said chimeric polypeptide has at least 97% identity with the reference sequence comprising SEQ ID NO: 435.
28. The AAV capsid protein of claim 17 , wherein said chimeric polypeptide has at least 99% identity with the reference sequence comprising SEQ ID NO: 435.